Abstract: Environment and Health Group, Tufts Infectious Disease Clinic, and Palmetto AIDS Life Support Services, will collaborate under the leadership of Patricia Weitzman, PhD, to develop and test the effectiveness of the first-ever individually-tailored, developmentally- and culturally-sensitive, mobile health (mhealth) PrEP adherence intervention called DOT. The intervention will target culturally-diverse, young adult men, ages 18-35, who have sex with men (YMSM). When the PrEP pill is taken daily, it can reduce HIV risk by 92-99%. The CDC estimates the daily PrEP pill is appropriate for 500,000 MSM in the U.S. Impact models show even modest increases in PrEP adherence could reduce new HIV infections among MSM by 29% over 20 years. The recent rise in HIV infection among young people, particularly minority YMSM, points to the value of PrEP uptake and adherence support for YMSM. In PrEP efficacy trials, younger age was the most consistent correlate with low PrEP adherence. Extensive mobile phone penetration among young adults makes mhealth an ideal, low-cost method for providing PrEP adherence support to culturally-diverse YMSM. Our DOT mhealth intervention reflects a developmental understanding of young adult decision-making, and is uniquely combined with principles from social cognitive theory, positive psychology and behavioral economics, all toward the goal of supporting PrEP adherence. The proposed project is based on Dr. Weitzman's successful Phase 1 trial of DOT, which led to significant improvements in PrEP adherence, PrEP treatment self-efficacy, and intention to follow PrEP treatment guidelines among the YMSM that used DOT for six weeks. Our proposed Phase 2 DOT mhealth intervention is directly responsive to Phase 1 findings by adding recommended new features and enhancements, including: 1) new texts targeting stress burden 2) new online community for social support 3) new linkage to the federal crisis text line 4) new gamification via a virtual avatar 5) new automatic time-zone adjustments 6) new cloud-based platform to view user engagement 7) new calendar for clinic appointments and pharmacy refills 8) enhanced personalization of pill reminders and 9) enhanced adherence graphing designed for sharing with healthcare providers. In Phase 2, we will test the effectiveness of DOT at improving PrEP adherence in a randomized controlled trial. Our goal is to help stop the rise in HIV among YMSM. Another potential benefit of DOT is advancement of the evidence base on how mhealth might address patient support issues in HIV prevention and other healthcare concerns toward the larger goal of reducing health disparities.